Substrate Modification to Increase the Enantioselectivity of Hydrolases. A Route to Optically-Active Cyclic Allylic Alcohols.

Article abstract of DOI:10.1016/S0957-4166(00)80126-3

The esterase-catalyzed resolution of the cyclic allylic acetates - 1-acetyloxy-2-cyclopentene, 1-acetyloxy-2-cyclohexene, and 1-acetyloxy-2-cycloheptene - was not enantioselective.We hypothesized that this inefficiency stems from the similarity in size of the substituents at the stereocenter (CH2-CH2 vs.CH=CH).To increase the enantioselectivity, we resolved precursors to these cyclic allylic alcohols: esters of trans-2-bromocycloalkanols (C5, C6, C7).These esters had a larger difference in the size of the substituents (CH2 vs.CHBr) at the stereocenter and were efficiently resolved by both cholesterol esterase and lipase from Pseudomonas cepacia (Amano P, PCL).A synthetic-scale resolution with PCL yielded the (1S,2S)-1-butanoyloxy-2-bromocycloalkanes in >98percent ee.Heating with DBU to eliminate HBr, followed by reduction with LiAlH4 to cleave the ester, yielded the allylic alcohols (S)-(-)-2-cyclopenten-1-ol (65percent ee), (S)-(-)-2-cyclohexen-1-ol (>99percent ee), and (S)-(-)-2-cyclohepten-1-ol (>98percent ee).